sponsor strategy decision

The study is a Phase 3 multi-centre, randomised, double-blind, parallel-arm study to evaluate the efficacy and safety of HLX01 versus European Union (EU)-sourced Mabthera® as first line treatment in patients with low tumour burden FL.

The study will consist of a Screening Period (up to 42 days), Treatment Period (Week 1 to Week 44/Month 11), and End of Study (EOS; Month 12 Visit). Approximately 212 patients (106 in each treatment group) will be enrolled.

Utilising a 1-sided 97.5% CI for the risk difference, a reference proportion of 83.2% for Mabthera®, delta for non-inferiority of -17%, and assuming a true difference of 1%, a sample size of 106 patients per arm (212 total) provides approximately 85% power to show non-inferiority of HLX01 to Mabthera® on a primary endpoint of risk difference in ORR up to Week 28. No dropout is included, as all patients will either have data provided for ORR (based on best response), or will be classed as non-responder.

Inclusion Criteria:

1. Voluntary written informed consent before any study-related activities
2. ≥ 18 years of age
3. Histologically-confirmed, stage II to IV NHL (CD20+ FL of grades 1, 2, or 3a) by World Health Organization classification of lymphoid neoplasms (2016 revision) [11]
4. Low tumour burden according to the GELF criteria
5. The Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
6. Availability of tumour sample within 12 months before start of study drug treatment
7. At least 1 bi-dimensionally measurable nodal lesion >1.5 cm or extranodal lesion >1 cm in its longest diameter by CT scan as defined by the Modified Lugano Response Classification 2014
8. Adequate organ function

Exclusion Criteria:

1. Prior treatment for FL. Patients previously treated with radiotherapy for stage I FL may be eligible provided they have a measurable lesion located outside the radiation field
2. Transformation to high-grade lymphoma
3. Patients with advanced disease that are considered for treatment with combined chemo immunotherapy
4. Presence or history of central nervous system (CNS) lymphoma involvement
5. Treatment with an investigational agent within 28 days of the first dose of study drug infusion
6. Prior treatment with a chimeric antibody, including HLX01 and Mabthera®
7. History of another malignancy within 2 years of screening, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ of the uterine cervix, breast or bladder, localised prostate cancer stage T1c or less - and provided that the patient remains relapse free
8. Major surgery within 28 days of the first dose of study drug infusion (excluding lymph node biopsy)
9. Known human immunodeficiency virus (HIV) infection (Serological test for HIV should be performed at screen unless prohibited by local regulations)
10. Active and/or severe infections, including any ongoing infection requiring IV anti microbial treatment
11. Have a current diagnosis of active tuberculosis
12. Active HBV and a positive serological test for HBV (except seropositive due to HBV vaccination) or hepatitis C virus (HCV)
13. Ongoing immunosuppressant treatment; corticosteroid treatment exceeding 20 mg/day prednisone or equivalent within 7 days of the first dose of study drug infusion
14. Known hypersensitivity or allergy to the active principle and/or formulations' ingredients; history of severe allergy or anaphylaxis to murine or biologic agents
15. Live or live attenuated vaccine within 28 days of the first dose of study drug infusion
16. History of significant cardiac or vascular disease including, but not limited to: history of stroke, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication or mechanical control within 6 months before randomisation; congestive heart failure according to the New York Heart Association (NYHA) Functional Classification class III or IV